Dose-escalation of CD19/CD22/BCMA CAR‑T for relapsed or refractory B‑cell non‑Hodgkin lymphoma
A Dose Escalating Study of CD19/CD22/BCMA Three Targets Autologous Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma(NHL)
This trial will try a CAR‑T therapy that targets CD19, CD22, and BCMA in people with relapsed or refractory B‑cell non‑Hodgkin lymphoma to find a safe dose.
Quick facts
| Phase | Early Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Shanghai Cell Therapy Group Co.,Ltd Industry-sponsored |
| Drugs / interventions | CAR-T, chemotherapy, chimeric antigen receptor |
| Locations | 1 site (Shanghai, Shanghai Municipality) |
| Trial ID | NCT06446128 on ClinicalTrials.gov |
What this trial studies
This is a single‑arm, open‑label, investigator‑initiated dose‑escalation study of autologous CAR‑T cells directed against CD19, CD22, and BCMA in patients with relapsed or refractory B‑cell non‑Hodgkin lymphoma. The primary goal is to define safety, tolerability, and the maximum tolerated dose; secondary objectives include pharmacokinetics, in vivo CAR‑T persistence, pharmacodynamics, and preliminary efficacy. Enrolled patients undergo screening, apheresis to collect cells, lymphodepletion chemotherapy, infusion of the engineered CAR‑T product on Day 0, and DLT monitoring through Day 28 followed by longer term follow-up. The protocol uses sequential dose cohorts to escalate dosing while monitoring for treatment‑related toxicities.
Who should consider this trial
Good fit: Adults with relapsed or refractory B‑cell non‑Hodgkin lymphoma (including DLBCL, PMBCL, transformed follicular lymphoma, and high‑grade B‑cell lymphomas) who meet protocol medical and organ‑function criteria and are candidates for autologous CAR‑T manufacturing may be eligible.
Not a fit: Patients with non‑B‑cell lymphomas, uncontrolled infections, severe organ dysfunction, active uncontrolled CNS disease, or who cannot undergo leukapheresis or travel to the study center are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, this approach could offer an additional therapy that induces remissions in patients whose B‑cell NHL has failed prior treatments.
How similar studies have performed: CD19‑directed CAR‑T therapies have produced durable remissions in many relapsed/refractory B‑cell lymphomas, while multi‑antigen CAR‑T approaches (including CD22 or BCMA co‑targets) are more experimental with limited but growing clinical data.
Eligibility criteria
Show full inclusion / exclusion criteria
Key Inclusion Criteria: * Patients who are diagnosed with relapsed/refractory B cell non-Hodgkin lymphoma , especially * Diffuse Large B Cell Lymphoma, not other specified (DLBCL,NOS), * Primary Mediastinal Large B Cell Lymphoma (PMBCL) * Transformation Follicular Lymphoma (TFL) * High grade B-cell lymphoma(HGBCL) * High grade B-cell lymphoma (HGBCL) with MYC(myelocytomatosis oncogene) and BCL2(B-cell lymphoma2) /BCL6 (B-cell lymphoma6) rearrangement * Refractory diseases are defined as one of the following * No response to last line of therapy: i. Progressive disease (PD) as best response to most recent therapy regimen; ii. Stable disease (SD) as best response to most recent therapy regimen * Not candidate for autologous stem cell transplant (ASCT) or refractory post-ASCT: i. Disease progression (PD) or relapsed ≤12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy * Individuals must have received adequate prior therapy including at a minimum: * anti-CD20 monoclonal antibody unless investigator determines that tumor is CD20-negative and * an anthracycline containing chemotherapy regimen * Immunohistochemical staining shows at least two of B cell surface receptor antigen CD19,CD20, BCMA are positive(including weak, medium and strong positive) * At least one measurable lesion during the screening based on the recommendation for initial evaluation, staging and response assessment of Hodgkin and non-Hodgkin lymphoma. * Life expectancy ≥ 12 weeks * Eastern cooperative oncology group (ECOG) performance status of 0 or 1 * Adequate renal, hepatic, pulmonary and cardiac function defined as: * Renal function: Serum creatinine ≤ 1.5 upper limit of normal(ULN), or eGFR ≥ 60 mL/min/1.73m2 \[eGFR(estimated glomerular filtration rate)=186×age\^-0.203×SCr\^-1.154（mg/dl）,female×0.742\] * Hepatic function: i: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 5 ULN and ii: total bilirubin ≤ 2 ULN, except in individuals with Gilbert syndrome (in Gilbert's syndrome patients, those with total bilirubin ≤ 3 ULN and direct bilirubin ≤ 1.5 ULN can be enrolled).iii: International normalized ratio (INR) or prothrombin time (PT) ≤1.5 ULN Pulmonary: Have the minimum level of pulmonary reserve, defined as ≤ CTCAE (Common Terminology Criteria for Adverse Events) grade 1 dyspnea and the SaO2(oxygen saturation)≥ 91% on room air * Cardiac: left ventricular ejection fraction (LVEF) ≥50% determined by echocardiogram(ECG) or multigated acquisition scan (MUGA) * Adequate bone marrow function, define as: * absolute neutrophil count (ANC) ≥1 ×10\^9/L * absolute lymphocyte count (ALC)≥ 0.5 ×10\^9/L * Platelets ≥50 ×109/L； * Hemoglobulin ≥80 g/L; patients with bone marrow involvement can be enrolled if globulin\>60 g/L * Female of child-bearing age and male participants must agree to use effective contraceptive methods until no CAR-T cells can be detected by PCR(polymerase chain reaction) test. Key Exclusion Criteria: * Individuals who have antiCD45 or antiCD3 therapy * Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of primary or secondary CNS (central nervous system) lymphoma, cerebrospinal fluid malignant cells or brain metastases * Presence or history of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement * History of allogeneic stem cell transplantation * Any of the following situations: • HBsAg/ HBeAg positive; HBeAb/HBcAb positive and HBV(hepatitis B virus) DNA copies above the lower test limit; * HCV(hepatitis C virus) RNA positive * HIV(human immunodeficiency virus) positive or treponema pallidum positive * Presence of active or life-threatening fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. * Individuals presence of unstable angina or myocardial infarction within 6 months of screening, or other severe/uncontrolled diseases during the screening (eg. Unstable or uncompensated respiratory, cardiac, hepatic or renal disease) * Presence of uncontrolled arrhythmia with treatment * Pregnancy or breastfeeding women Other protocol defined inclusion/exclusion criteria may apply.
Where this trial is running
Shanghai, Shanghai Municipality
- Mengchao Cancer Hospital — Shanghai, Shanghai Municipality, China (Recruiting)
Study contacts
- Principal investigator: Jinxing Lou — Shanghai Mengchao Cancer Hospital
- Study coordinator: Jinxing Lou
- Email: loujx@shcell.com
- Phone: 021-67091399
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.